Introduction

This year was the BioProcess International Conference (BPI West’s) inaugural year. I was excited to attend and to see what the format for the new conference was going to be. I felt that the content was very relevant and covered a wide breadth of topics, from drug development to commercial manufacturing. BPI West delivered talks focused on improving the manufacturing process for biopharmaceuticals, enabled industry networking opportunities, and provided the chance to see the latest products and technologies.

BioProcess International Conference Highlights – Keynotes

Innovative strategies for biotherapeutic development and manufacturing

For me there were several highlights of BPI West, but one feature that I always enjoy are the keynote talks. BPI West’s keynotes were no exception. The first keynote was given by Amita Goel, MSc., Founder and CEO, Celltheon, and was titled “Innovative Technologies for the Expression of Next Generation Bio Therapeutics.” In the talk Ms. Goel discussed the need for new and innovative technologies in the development and manufacturing of biotherapeutics to meet the goal of bringing biopharmaceuticals to market faster and at less cost. Ms. Goel began her talk with an interesting history of the development of current biomanufacturing practices and then moved on to discuss ways to improve this process.

One method for improvement that Ms. Goel discussed was the use of genomics to improve expression. She discussed how Celltheon has developed the SMART technology platform that has provided improvements to cell line development, process development and optimization for their clients. As an example she discussed their genomics based expression vector where they have been able to achieve 2.5x increases in expression with no amplification. By employing their technology platform they have also been able to shorten the timeline to preclinical material to 5-6 weeks. Ms. Goel stressed the importance of using a systems biology approach and employing innovative technologies to bring products to market faster and in a more cost-effective manner.

Employing process development capabilities for a modality independent strategy

The next keynote was presented by Rohini Deshpande, Ph.D., Executive Director, Process and Product Development, Amgen and was titled, “Adapting Process Development Capabilities for a Modality Independent Strategy.” Dr. Deshpande delivered an excellent talk about the challenges facing biopharmaceutical companies who are manufacturing different types of therapeutics. As Dr. Deshpande described, Amgen has a great deal of diversity in their pipeline including bi-specific antibodies, fusion proteins, antibody-drug conjugates, immunotherapy virus, and as a result of the Kite Pharma collaboration cell based therapies. Recent product launches have reflected this diversity including Kyprolis (small molecule), Repatha (MAb), Blincyto (BITE – Bi-specific T-cell engagement), and Imlygic (live virus therapy). In her talk Dr. Deshpande discussed how Amgen has had to adapt process development for a modality independent strategy and implementation of their “Patient Centric Process Development” approach.

Single-use Technologies

Adam Goldstein, MSc., Principal Scientist, Single Use Technologies, Global Manufacturing Sciences, Genentech, Inc. delivered the final keynote titled, “Single Use Facilities in Emerging Markets.” In his keynote, Mr. Goldstein did an excellent job discussing items to consider when thinking about implementing single-use strategies and why they are so attractive in an emerging market. While stainless steel is still the primary manufacturing method for commercial products, single-use is growing and has already demonstrated proof of principle in pre-commercial and some commercial operations.

Mr. Goldstein also presented relevant case studies that have been used to determine the “sweet spot” for single-use technologies (SUT) including considerations of:

• Cost per gram vs. titer and scale
• True cost of ownership for steel vs. plastic
• Recommended products like BioSolve software to model and provide cost analysis for stainless steel vs. single-use facilities.
• Key variables for SUT decision – run rate, change over, multi-product, and scale

Next Mr. Goldstein explored the concept of facilities of the future. He made the point that with more targeted therapies in smaller niche populations, biopharmaceutical companies will need to manufacture a larger number of products in the same facility, which means there will be more change over. In these situations single-use can provide real benefits.

Another facility of the future concept is the modular facility. The use of disposables in flexible modular facilities permits more geographical flexibility for manufacturing. This enables manufacturing to take place closer to customers and to demand. One method for achieving this is to place pre-made, small modular manufacturing units in various geographical locations, i.e. closer to customers, in emerging markets, to address a specific crisis, etc. These units are available today and are manufactured by companies including GE Healthcare, Kubio and G-Con. Because they are modular, these units can be employed rapidly and allow for increased flexibility and capacity to meet changes in demand locally or in emerging markets.

While identifying several advantages, Mr. Goldstein also identified areas for improvement with respect to SUT implementation including:

• Improved products for downstream applications
• Standardization of single-use technologies – currently no set standard amongst vendors or industry
• Assurance of supply – improve procurement standards
• Knowledge management – shared data system for industry to share SUT data
• RHA risk assessment for extractables and leachables needs improvement – still difficult and time consuming

BioProcess International Discussions by Conference Track

There were some overall themes this year that I felt were a continuation of many great discussions that were presented at the BPI East Conference last fall including continuous processing in both upstream and downstream and CHO media development and optimization. This is by no means an exhaustive list, but some highlights of the talks I attended by track include:

Basic Research and Discovery

• High throughput methods for lead identification
• Developing formulation and predicting formulation success in selection stage
• Detecting toxicity issues early and other IND considerations to prepare for early
• Best practices for transitioning from research and discovery into development

Early Stage Process Development

• Several talks on novel approaches to cell line development
• Great discussions around identifying causes of variability in cell culture media and how they can affect glycosylation and charge variants
• Importance of considering media ingredients when looking at product quality attributes
• Use of analytical tools for in-process monitoring
• Continuous processing in both upstream and downstream
• Several discussions around using new recovery and purification technologies to improve overall efficiency and purification
• High throughput process development strategies
• Implementing PAT tools and applying QbD

Late Stage Process Development

• Next generation bioprocessing strategies including an end to end continuous processing approach
• Limiting aggregates in final purified products
• Best practices for process scale up and transfer
• Best practices for tech transfer for commercial manufacturing and across global manufacturing networks.
• Data collection, data management and bioprocess automation
• Talks on integrating critical quality attribute monitoring and multi-attribute monitoring and control

Commercial Manufacturing and Beyond

• Streamlining and integrating drug substance and final drug product manufacturing
• Facility design incorporating the ballroom suite or central manufacturing suite approach.
• Closed systems as a way to enable more flexible facilities, see “Closed Systems in Biomanufacturing Offer A Variety of Benefits,” for more information.
• Reducing timelines and meeting increasing demands for commercial manufacturing
• Many talks on biosimilars and product quality, characterization and comparability.
• Good discussion on supplier relationships and ensuring raw material tracking and control.

I will cover several of these areas in more detail in the coming weeks – stay tuned.

Additional BPI West Coverage:

• Upstream Continuous Process – Perfusion Culture